Background: The importance of self-breast examination (SBE) to identify early signs of breast abnormality and as a significant preventative practice for early identification of breast cancer have been widely recognized among the scientific community. However, in many developing countries with varied health care practices, women’s understanding about knowledge, attitudes, and practices (KAP) of SBE is still far from known. In the present study, we made a comparative analysis of KAP of SBE among women in Mexico and Nicaragua.  Methods: We conducted a cross-sectional survey of women aged 18 years and over living in selected urban and rural areas of the State of Jalisco, Mexico (n=547) and Nicaragua (n=500). Measures included in the survey reflected KAP related to SBE. We compared these measures between women living in urban and rural areas and women aged 18-39 years and 40+ years in both countries. Using t-tests, we evaluated the significance of these differentials.  Results: Study results indicated widespread and significant differentials in basic knowledge and behaviors on SBE practices among women living in rural and urban locations both in Mexico and in Nicaragua. For example, while younger women reported significant and lower overall knowledge about breast cancer (BC), and purpose and reasons for SBE compared to women who were in the 40+ age group in Nicaragua, however, there is no significant difference in knowledge, attitudes, behavior, and practices regarding self-breast examination between women living in urban and in rural areas of Jalisco, Mexico.  Conclusions: Study results call for location and population-specific programs and policies addressing disparities in breast cancer prevention and detection efforts in each country. While Jalisco has taken significant steps toward promoting cancer prevention, further attention to women in the older cohort is recommended, particularly for geographical relocation of mammography equipment and technicians.